AIMS: This goal of this study is to define and contrast the pharmacodynamic effects of physiologic and supraphysiologic testosterone (T) doses on the hypothalamic-pituitary-testicular axis, hepatic function, and psychosexual function. METHODS: This study will use a double-blind design to test 6 hypotheses that include: 1) prolonged administration of supraphysiologic doses of T in men causes a suppression of the pituitary gonadal axis which gives rise to a state of transient hypogonadism after drug withdrawal, 2) the hypogonadism which accompanies T withdrawal results from a defect in hypothalamic rather than pituitary or testicular function, 3) administration of supraphysiologic doses of T in men increases the level of aggression that correlates with the increased serum T concentrations, 4) the temporary hypogonadism which accompanies T withdrawal results in dysphoria that correlates with the decreased serum concentrations of T, 5) testosterone cypionate (TC) at both physiologic and supraphysiologic doses is eliminated as a first order kinetic elimination process, and 6) prolonged administration of supraphysiologic doses of T in men produces prolonged changes in subjects' T laboratory endocrine parameters that have greater sensitivity and specificity for identification of abuse than traditional urine screens. Thirty normal- subject volunteers naive to anabolic steroids, following a 2 week placebo lead-in, will be randomly assigned to receive TC weekly doses of 100, 250, or 500 mg for 14 consecutive weeks. Subjects will then receive 12 consecutive weekly placebo injections to examine the withdrawal effects TC. Biweekly laboratory studies will include a general chemistry screen, serum and urinary steroid assays, lipid screening, liver function tests, and thyroid function tests. Psychiatric symptomatology will be prospectively monitored biweekly using self-report measures and single- blind observatiorial measures. Measures will include the Buss-Durkee Hostility Inventory, the Scale for Suicidal Ideation, Hamilton Depression and Anxiety Scales, Modified Manic State Rating Scale, and the Brief Psychiatric Rating Scale and the Symptom Checklist 90. Urine drugs screens will be repeated every fourth week. All subjects will be monitored closely during the study for medical and psychiatric complications of T use. Subjects demonstrating significant medical or psychiatric dysfunction will be discontinued from the study and referred for further medical or psychiatric evaluation. IMPLICATIONS: This study will l) characterize the long-term sequelae and short-term neuropsychiatric and biomedical effects of the use of physiologic and supraphysiologic T doses and 2) improve techniques for analytical testing of AAS covert usage.